These studies are concerned with the regulation of plasma choline in the dog and chicken and particularly the role of the kidney in this regulation. By means of an enzymatic radiochemical microassay, choline is measured directly in plasma and urine. Evidence was obtained to suggest bidirectional active transport of choline by the renal tubule. At the same time the kidney metabolized choline to betaine. Loading studies in chickens at steady state revealed that total plasma clearance was regulated by a positive feedback at increasing intravenous loads, while urinary clearance operated as a negative feedback system. The perfused rat kidney excreted choline by active transport and this transport was inhibited by hemicholinium (HC-3).